Dry gel composition

ABSTRACT

There is provided a dry gel composition comprising 40% by weight or below of a medicine which can be orally administered, 3% by weight or above of a gelling agent and 5% by weight or below of a binder, which composition is capable of forming a gruel-like aqueous gel composition upon mixing with 2 to 15 parts by weight of water per part by weight of the composition at a temperature of 40° C. or below. The gelling agent usable herein is, for example, pregelatinized starch having a concentration of 50% by weight or above. The medicine which can be orally administered is, for example, cinnarizine. Upon mixing with a predetermined quantity of water, the dry gel composition forms a homogeneous aqueous gel composition having a viscosity of about 100 to 500 cp, which is preferably thixotropic. Even aged people having a weak swallowing function can easily swallow the aqueous gel composition, without causing improper sucking into their tracheas. Thus, the dry gel composition of the present invention is very useful in their medical care. The aqueous gel composition can be prepared in a short time by an extremely simple operation at the time of use.

TECHNICAL FIELD

The present invention relates to a dry gel composition containing amedicine which can be orally administered and capable of forming agruel-like gel composition upon mixing with a predetermined quantity ofwater at the time of use.

BACKGROUND OF THE INVENTION

As aged people are increasing in number in the population recently,there is a growing interest in their medical care. The swallowingfunction in the aged people is generally lower than that of youngerhealthier people, and it is not easy for them to swallow solidpreparations such as tablets and capsules. Thus, it has been usuallydifficult to administer medicines, which are similar to those to begiven to people in the prime of life, to the aged people. In the medicaltreatment of the aged people, the patients often have two or morediseases to be treated and usually two or more kinds of medicinesincluding the solid preparations are prescribed for them. Thus, theswallowing of the medicines having different shapes often caused muchlabor and pain for them. It was proposed under these circumstances toadminister a liquid preparation such as a syrup instead of the solidcapsules in the pharmacotherapy of the aged people. However, theadministration must be carefully carried out, since the reflectivefunction in the bifurcation of trachea of the aged people is generallyweak, and the liquid might be partially sucked in the trachea at thetime of the swallowing. Particularly when an aged patient is nursed athome, serious problems such as dyspnea due to improper suction are oftencaused.

Therefore, the object of the present invention is to provide acomposition from which a preparation which can be easily swallowed byaged people can be prepared at the time of use.

In particular, the object of the present invention is to provide a drygel composition containing a medicine which can be orally administeredand capable of rapidly forming an aqueous gel composition upon mixingwith a predetermined quantity of water without heating at the time ofuse.

DISCLOSURE OF THE INVENTION

After intensive investigations made for the purpose of solving theabove-described problems, the inventor has found that a gruel-likecomposition comprising a gel structure easily causes the swallowingreflex and, therefore, such a composition can be swallowed by even agedpeople having a weakened swallowing function without causing theimproper suction in the trachea. The inventor has also found that thegel composition can be easily prepared from a dry gel compositioncontaining a gelling agent capable of rapidly forming a gel upon mixingwith water at 40° C. or below. The present invention has been completedon the basis of these findings.

Namely, the present invention provides a dry gel composition comprising40% by weight or below, based on the whole composition, of a medicinewhich can be orally administered, 3% by weight or above of a gellingagent and 5% by weight or below of a binder, which composition iscapable of forming an aqueous gruel-like gel composition upon mixingwith 2 to 15 parts by weight of water per part by weight of thecomposition.

In an embodiment of the present invention, the dry gel compositioncomprises 40% by weight or below of a medicine which can be orallyadministered, 50% by weight or above of pregelatinized starch and 5% byweight or below of a binder, which composition is capable of forming anaqueous gruel-like gel composition upon mixing with 6 to 8 parts byweight of water per part by weight of the composition.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a hysteresis curve obtained by mixing 1 part by weight ofcomposition 7 given in Table 1 with 8 parts by weight of water, leavingthe mixture to stand for 60 min and determining the relationship betweenshear stress of the aqueous gel composition and the shear rate with acone plate-type rotational viscometer.

FIG. 2 shows a hysteresis curve obtained by mixing 1 part by weight ofcomposition 6 given in Table 1 with 8 parts by weight of water, leavingthe mixture to stand for 60 min and determining the relationship betweenshear stress of the aqueous gel composition and the shear rate with acone plate-type rotational viscometer.

FIG. 3 shows a hysteresis curve obtained by mixing 1 part by weight ofcomposition 12 given in Table 4 with 3 parts by weight of water, leavingthe mixture to stand for 60 min and determining the relationship betweenshear stress of the aqueous gel composition and the shear rate with acone plate-type rotational viscometer.

THE BEST EMBODIMENT FOR CARRYING-OUT THE INVENTION

When a specified quantity of water is added to the dry gel compositionof the present invention and the resultant mixture is stirred at atemperature of 40° C. or below, preferably at 15° to 25° C., thecomposition is swollen, becomes bulky and forms an aqueous gelcomposition.

The term "gelation" generally indicates that colloidal particlesdispersed in a dispersion medium are collected together by means oftheir affinity to form a secondary structure. The aqueous gelcomposition obtained by stirring the dry gel composition of the presentinvention with water has a structural viscosity. The aqueous gelcomposition preferably has thixotropic properties. The term "thixotropicproperties" indicates such properties that when a mechanical stress isapplied to the aqueous gel composition under isothermal conditions, itsgel structure is broken to lower the viscosity but, after leaving thecomposition to stand for a while, the gel structure is regenerated torecover its viscosity. It is preferred that the aqueous gel compositionis thixotropic since when the dry gel composition of the presentinvention is mixed with water in such a case, an intended aqueous gelcomposition is obtained with a high reproducibility irrespective of themixing strength or mixing time.

The properties of the aqueous gel composition obtained from the dry gelcomposition of the present invention can be determined by examining therelationship between the viscosity of the aqueous gel composition andthe shear rate with, for example, a cone plate-type rotationalviscometer and observing the change in the shear stress of the aqueousgel composition by the change in the stress from the hysteresis curve.Examples of the hysteresis curves of the aqueous gel compositionsobtained from the dry gel compositions of the present invention aregiven in FIGS. 1 to 3.

The fact that the flow curve representing the relationship between therotation speed and torque rises as the rotation speed is elevatedindicates that since the shear deformation speed of the sample iselevated as the rotation speed rises, the breaking of the structure inthe aqueous gel composition is accelerated to lower the apparentviscosity. Thus, the higher the degree of the arching of the curveshowing the hysteresis of the viscosity, the higher the degree ofbreaking of the gel structure by the mechanical stress. Therefore, itcan be employed as an index of the degree of thixotropy. Where the gelstructure broken as the rotation speed is reduced in the aqueous gelcomposition is not rapidly regenerated, the apparent viscosity isunchanged and, therefore, the area made by the hysteresis curve islarge. Such an aqueous gel composition is preferred, since it keeps itsfluidity even after the structure has been broken by mastication to makethe swallowing easy. On the contrary, where the gel structure broken asthe rotation speed is reduced in the aqueous gel composition is rapidlyregenerated, the area made by the hysteresis curve is small. Theproperties of such an aqueous gel composition are shown in FIG. 3.

The gelling agent contained in the dry gel composition of the presentinvention is a substance which imparts the above-described properties tothe dry gel composition of the present invention. In particular, thegelling agent is a substance which rapidly forms a gel upon mixing withwater in a quantity of the maximum absorption or below at a temperatureof 40° C. or below, preferably 15° to 25° C. The gelling agent ispreferably a thixotrope, i.e. a substance capable of forming athixotropic gel under the above-described conditions. The gelling agentswhich can be contained in the composition of the present inventioninclude, for example, pregelatinized starch, sodium starch phosphate,carrageenin, locust bean gum, a mixture of carrageenin and locust beangum, carboxymethylated starch, a mixture of LM pectin and a calciumion-containing substance, or an acid substance, guar gum, a mixture oflow substituted hydroxypropyl cellulose and sodium carboxymethylcellulose, tragacanth powder, bentonite, a mixture of bentonite andsodium carboxymethyl cellulose, and a mixture of crystalline celluloseand sodium carboxymethyl cellulose. The gelling agents are not limitedto them. Among them, pregelatinized starch is preferably used.

The term "pregelatinized starch" herein indicates a starch which formsno interference band in X-ray analysis. Pregelatinized starch can beprepared by, for example, a method wherein starch particles are heatedtogether with water, a method wherein starch is treated with a swellingagent such as a calcium nitrate or sodium hydroxide solution, or amethod wherein starch is etherified or esterified with phosphorusoxychloride. Pregelatinized starch prepared as described above can bedried at a temperature of, for example, 80° C. or above to reduce thewater content thereof to 15% or below before the use. Still preferredpregelatinized starch used in the present invention is, for example,that prepared from corn starch by hot roll method. Such a product isavailable from, for example, Matsutani ChemicalsIndustries Co., Ltd.Such an pregelatinized starch has a water content of usually 13% byweight or below, preferably 10% by weight or below, and a particle sizeof 150 μm or below.

Other gelling agents usable in the present invention are also availableon the market. For example, Pionil 1500 (a product of Matsutani ChemicalIndustries Co., Ltd.) is used as the sodium starch phosphate, GENU GELSWG-J (a product of Copenhagen Pectin Factory) is used as thecarrageenin; Primojel (a product of Matsutani Chemical Industries Co.,Ltd.) is used. as the carboxymethylated starch; GENU pectin is used asthe LM pectin, guaiacol is used as the guar gum; L-HPC(LH-31) andL-HPC(LH-21) are used as the low substituted hydroxypropyl cellulose;and Avicel RC-591NF is used as the mixture of crystalline cellulose andsodium carboxymethyl cellulose.

The medicine contained in the dry gel composition of the presentinvention is any of those which can be orally administered and dissolvedand absorbed to exhibit its effect in the gastrointestinal tract.Examples of these medicines include antipyretic and analgesic agentssuch as ibuprofen and fenbufen; antivertigo agents such as betahistineand difenidol; neurotropic agents such as imipramine, amitriptyline,diazepam, haloperidol and timiperone; comprehensive cold remedies suchas promethazine, saliycylamide, acetaminophen and anhydrous caffeine;medicines for central nerves such as idebenone; skeletal musclerelaxants such as dantrolene and chlorphenesin; antispastic agents suchas afloqualone and eperisone; cardiotonic agents such as digitalis anddigoxin; remedies for arrhythmia such as procaineamide, atenolol,pindolol and propranolol; diuretics such as hydrochlorothiazide andfurosemide; hypotensive agents such as captopril, prazosin andmethyldopa; vasodilator drugs such as dipyridamole, diltiazem, trapidil,nifedipine and isosorbide; medicines for diseases of the cardiovascularsystem such as vinpocetine, ifenprodil, pentoxifylline, nicardipine,cinnarizine and dihydroergotoxine; antitussives and expectorants such asdextromethorphan; medicines for peptic ulcer such as dicyclomine andteprenone; antacids such as magnesium oxide and sodiumhydrogencarbonate; purgatives such as sennoside; hormone drugs such askallidinogenase; vitamins such as alfacalcidol, benfotiamine, pyridoxineand cyanocobalamine; calcium drugs such as calcium lactate; hematicmedicines such as ticlopidine; medicines for gout such as allopurinol;and medicines for malignant tumors such as tegafur. The medicines anddrugs usable in the present invention are by no means limited to them.These medicines and drugs can be used either singly or in combination oftwo or more of them. Acid-addition salts and base-addition salts of themare also usable. The acid-addition salts include, for example,hydrochloride, sulfate, hydrobromide, methanesulfonate, lactate andcarbamate. The base-addition salts include, for example, metal saltssuch as sodium, potassium, magnesium and calcium salts, ammonium saltand amine-adduct.

The binders which can be contained in the dry gel composition of thepresent invention include, for example, hydroxypropyl cellulose,hydroxypropyl methylcellulose and polyvinylpyrrolidone.

The dry gel composition of the present invention contains 40% by weightor below, based on the composition, of the medicine which can be orallyadministered, 3% by weight or above) preferably 10% by weight or above,based on the composition, of the gelling agent and 5% by weight orbelow, based on the composition, of the binder. In a preferredembodiment of the present invention, the dry gel composition containingpregelatinized starch as the gelling agent contains 40% by weight orbelow, based on the composition, of the medicine which can be orallyadministered, 50% by weight or above, preferably 60% by weight or above,based on the composition, of pregelatinized starch as the gelling agentand 5% by weight or below, based on the composition, of the binder.

When 1 part by weight of the dry gel composition of the presentinvention is mixed with 2 to 15 parts by weight of water, it is swollen,becomes bulky and forms an aqueous gel composition. The aqueous gelcomposition thus obtained generally has a gruel-like appearance, aself-fluidity and a viscosity of, for example, about 100 to 500 cP. Thequantity of water to be added in order to obtain such an aqueous gelcomposition is suitably selected in the above-described range dependingon the power of the gelling agent and the relative amount of the gellingagent to the dry gel composition. For example, when a gelling agenthaving a strong gelling power such as a mixture of crystalline celluloseand sodium carboxymethyl cellulose (Avicel RC-591NF) is used, therelative amount of the gelling agent to water is reduced, and when agelling agent having a weak gelling power such as pregelatinized starchis used, the relative amount of the gelling agent to water is increased.Water may be added to the dry gel composition at once or in portions.After the addition of water, the resultant mixture is stirred asimmediately as possible for 1 to 2 min until the homogeneous aqueous gelcomposition has been obtained. The stirring is conducted with a spoon orthe like at a temperature of 40° C. or below, preferably at roomtemperature.

In a preferred embodiment of the present invention, 1 part by weight ofthe dry gel composition containing at least 50% by weight, based on thecomposition, of pregelatinized starch is mixed with 6 to 8 parts byweight of water to form a thixotropic aqueous gel composition. Thevolume of thus swollen aqueous gel composition is 3 to 3.5 times aslarge as that of the dry gel composition. When the dry gel compositionof the present invention is used, it is preferred that the aqueous gelcomposition having such properties is prepared and administered to thepatient. When the quantity of water to be added is smaller than thisrange, the aqueous gel composition is converted into a substance whichlooks like dumplings made of rice powder or custard puddings in a fewminutes. On the other hand, when it is larger than this range, theresultant aqueous gel composition looks like a thin rice gruel. Both ofsuch aqueous gel compositions prepared from the dry gel composition ofthe present invention are usable. The custard pudding-like aqueous gelcomposition is suitable for patients having a relatively normalswallowing function, and the thin rice gruel-like aqueous gelcomposition is suitable also for tubal feeding. Various aqueous gelcompositions can be selectively prepared by controlling the quantity ofwater to be added depending on the conditions of the patient, whichmakes the adequate administration of medicine possible.

The dry gel composition of the present invention may contain, inaddition to the above-described components, excipients such as lactoseand D-mannitol; wetting agents such as glycols, e.g. polyethylene glycoland glycerol; surfactants such as Tween; thickening agents such assodium carboxymethyl cellulose and guar gum; and carbonates,hydrogencarbonates and organic acids which cause foaming upon additionof water at the time of use. The carbonates and hydrogencarbonatesinclude, for example, potassium carbonate, sodium carbonate, calciumcarbonate and sodium hydrogencarbonate, and the organic acids include,for example, citric acid, tartaric acid and malic acid. The foamingagent is preferably used in order to make the aqueous gel bulky. Otheradditives usable herein include disintegrators, pH adjustors,stabilizers, sweetening agents, flavors and colorants. When a gellingagent having a strong gelling power is used, the quantity thereof isonly small and, therefore, it is preferred to increase the proportion ofthe excipient so as to make the whole composition bulky. When themedicine for the oral administration contained in the dry gelcomposition of the present invention is bitter, a masking agent for thebitterness can also be used. The masking agents include, for example,glycols such as propylene glycol, glycerol and polyethylene glycol; andtaste-improvers such as potassium glutamate and sodium inosinate.Another method can also be employed, wherein a solid bitter medicine ispreviously finely pulverized and the surface of the particles is coatedwith a masking agent. Examples of preferred coating agents includewater-insoluble ethyl cellulose and hydroxypropyl methylcellulosephthalate.

The dry gel of the present invention is preferably granulated into agranule size of about 100 to 300 μm. The granulation can be conducted byan ordinary method with an organic solvent such as an alcohol, e.g.ethanol or propanol, a chlorinated hydrocarbon, e.g. methylene chloride,a mixture of them, or a mixture of such an organic solvent and water.The granulated dry gel composition of the present invention isadvantageous, since when water is added, at the time of use, to thecomposition, it gels very easily. The dry gel composition usually has awater content of 10% by weight or below before the granulation and 5% byweight or below at the time of the granulation. The dry gel compositionof the present invention thus granulated may be further tableted. Thetablets of the dry gel composition of the present invention thusprepared are preferred when the dose is to be controlled by counting.When the composition is to be tableted, an excipient and a disintegratorare usable. They are suitably selected by those skilled in the artdepending on the components and the use of the dry gel composition ofthe present invention.

The dry gel of the present invention can be produced by, for example,the following method by means of a high-performance stirring/granulatingmachine (such as NGSD-350; a product of Daiwa Kakoki) capable of mixingand kneading the powders by rotating blades fixed on a rotating shaftand also capable of granulating by aggregation, shearing, tumbling andgrading to form the granules: the starting medicine to be orallyadministered, a gelling agent such as pregelatinized starch and theexcipient are fed into a stirring tank, and they are mixed by rotatingthe blades of the granulating machine at a rate of about 100 to 200 rpm.The binder is added to the mixture, and the resultant mixture is stirredwith the blades rotating at an increased rate of about 300 to 500 rpm toform the granules. The granules thus obtained are dried with an airdryer at, for example, 40° C. for about 5 to 7 hours. The granules arethen sieved to obtain the dry gel composition of the present invention.The dry gel composition thus obtained is stable even after storage at60° C. for two months.

The following Examples will further illustrate the present invention,which by no means limit the invention.

EXAMPLE 1

The dry gel composition of the present invention was produced with ahigh-performance granulating machine (NGSD-350; a product of DaiwaKakoki; New gramachine, capacity: 33 l) having two lower scraping bladesand two upper flat blades fixed in this order on the rotating shaft insuch manner of crossing at sight angles. Predetermined quantities of themedicine to be orally administered and pregelatinized starch were fedinto the stirring tank and they were stirred with the blades at 100 rpmfor 10 min and then at 200 rpm for additional 10 min. Then the binderwas added thereto while the rotation rate was kept at 200 rpm, andthereafter the rotation rate was elevated to 300 rpm while thegranulation state was observed. The addition of the binder was completedin 5 min. After the completion of the addition of the binder, therotation rate was gradually elevated from 300 rpm to 500 rpm. Thegranulation was completed after about 5 to 8 min, and the granules wererecovered. The granules were dried with an air dryer (shelf type) at 40°C. for 5 to 7 hours, and then sieved through a 1000 μm sieve to obtainthe dry gel composition of the present invention. The compositions thusobtained are given in the following Table 1.

                  TABLE 1    ______________________________________    Composition No.               1       2      3    4    5    6    7    ______________________________________    Cinnarizine               286 g   286    300  300  300  --   --    Allopurinol               --      --     --   --   --   600  600    Pregelatinized starch    Matsunorin 1,400 g --     --   1,440                                        --   1,560                                                  --    CM.sup.1)    Matsunorin W.sup.2)               --      1,400  1,440                                   --   1,440                                             --   1,560    Binder TC-5               35 g    35     36   36   36   36   36    "S".sup.3)    Lactose 200M.sup.4)               390 g   390    444  444  444  120  120    D-Mannitol 175 g   175    180  180  180  84   84    Composition of               7.2     7.2    7.2  7.2  7.2  7.2  7.2    binder (for gradu-    lation) Conc. (%)    Amount (wt.) of               35 g    35     36   36   36   36   36    TC-5 "S"    Anhydrous  410 g   410    422  422  422  422  422    ethanol    Water      41 g    41     42   42   42   42   42    Recovery    1000 μm on               27 g    17     10   29   4    15   5    1000 μm pass               2,245 g 2,268  2,394                                   2,354                                        2,406                                             2,376                                                  2,385    Granular size distribution [1000 μm pass:sieving    method (%) n = 3]    850 μm on               1.6     1.0    1.0  2.3  0.6  1.3  0.7    500 μm on               9.4     6.3    5.1  11.8 4.6  8.3  4.2    250 μm on               12.5    9.7    8.1  16.2 7.6  12.9 7.8    150 μm on               41.8    32.8   30.1 40.2 29.7 40.4 18.9     75 μm on               31.9    45.3   49.7 26.8 51.5 33.0 58.0     75 μm pass               2.7     5.0    6.0  2.7  6.0  4.2  10.4    ______________________________________     .sup.1) Matsunorin CM: pregelatinized starch from corn starch; a product     of Matsutani Chemical Industries Co., Ltd.     .sup.2) Matsunorin W: pregelatinized starch from wheat starch; a product     of Matsutani Chemical Industries Co., Ltd.     .sup.3) Binder TC5 "S": hydroxypropyl methylcellulose; a product of     ShinEtsu Chemical Co., Ltd.,     .sup.4) lactose 200: 200 meshpassed lactose.

Water was added to each of the compositions shown in Table 1 to obtain agruel-like aqueous gel composition. The properties of the aqueous gelcomposition were determined under the following conditions:

Apparatus used: rheometer NRM-120 (a product of Nippon RheologyKabushiki Kaisha),

Standard solution for calibration of viscometer: JIS Z 9909 JS 200 (Lot24) (a product of Showa Shell Sekiyu K.K.),

Determination conditions:

Temperature: 20° C.

Shear rate: 1800 s⁻¹ (100 rpm)

Program time: 60 s .

Sample-preparation method: 8, 12, 14 or 16 ml of purified water wasadded to 2 g of the sample, and the mixture was stirred for 2 min.

Measurement intervals: after 5 min, 10 min and 60 min. Frequency ofmeasurement: continuous repeated measurement (3 times) for each sample.

Point of time of measurement: The viscosity was determined at themaximum shear rate.

The results are given in the following Tables 2 and 3.

                  TABLE 2    ______________________________________    Preparation No.                1    ______________________________________                First       Second  Third    5 min. after                266         264     264    1:6 30 min. after                288         288     287    60 min. after                --          --      --    ______________________________________    Preparation No.                2    ______________________________________                First       Second  Third    5 min. after                306         328     320    1:6 30 min. after                398         360     331    60 min. after                527         439     392    ______________________________________    Preparation No.                3    ______________________________________                First       Second  Third    5 min. after                291         327     322    1:6 30 min. after                362         342     320    60 min. after                470         410     360    ______________________________________

                  TABLE 3    ______________________________________    Preparation No.              4              5    ______________________________________              First  Second  Third First Second                                               Third    5 min. after              1492   1378    1318  1151  1015  921    1:4 30 min. after              1268   1272    1238  1171  1175  1091    60 min. after              1068   1332    1248  1228  1125  1038    5 min. after              210    208     208   282   310   302    1:6 30 min. after              224    226     232   362   327   299    60 min. after              306    306     307   429   344   326    5 min. after              117    119     119   132   130   132    1:7 30 min. after              109    99      93    190   178   174    60 min. after              117    104     100   165   162   157    5 min. after              66     56      53    72    66    65    1:8 30 min. after              71     59      55    88    85    86    60 min. after              74     59      53    101   94    89    ______________________________________    Preparation No.              6              7    ______________________________________              First  Second  Third First Second                                               Third    5 min. after              1725   1478    1375  1562  1402  1272    1:4 30 min. after              1368   1352    1252  1378  1422  1318    60 min. after              2137   1949    1795  1445  1298  1201    5 min. after              272    272     264   429   391   356    1:6 30 min. after              259    270     268   563   443   400    60 min. after              379    351     332   725   561   502    5 min. after              138    135     135   256   229   216    1:7 30 min. after              221    189     178   394   364   341    60 min. after              236    212     202   352   329   254    5 min. after              101    101     101   136   132   135    1:8 30 min. after              70     55      53    121   118   115    60 min. after              96     73      65    232   184   159    ______________________________________

EXAMPLE 2

The dry gel compositions of the present invention given in the followingTable 4 were prepared in the same manner as that of Example 1.Composition No. 17 was prepared by adding low substituted hydroxypropylcellulose as the disintegrator to the granules prepared as describedabove and tableting the resultant mixture with an autograph (a productof Shimadzu Corporation) to obtain raw tablets each containing 50 mg ofcinnarizine.

EXAMPLE 3

The dry gel compositions of the present invention given in the followingTable 5 were prepared in the same manner as that of Example 1.Composition No. 21 was prepared by tableting in the same manner as thatfor the composition No. 17 to obtain raw tablets each containing 50 mgof cinnarizine.

                                      TABLE 4    __________________________________________________________________________    Composition No.              8   9    10  11  12  13   14   15   16   17    __________________________________________________________________________    Cinnarizine               50 mg                  50 mg                        50 mg                            50 mg                                50 mg                                   50 mg                                        50 mg                                             50 mg                                                  50 mg                                                        50 mg    Pionil 1500.sup.1)              --  260 mg                       --  --  --  --   --   --   --   --    Genu gel SWG-J.sup.2)              --  --    40 mg                           --  --  --   --   --   --    5 mg    Locust bean gum              --  --    80 mg                           --  --  --   --   --   --    10 mg    Primojel.sup.3)              --  --   --  130 mg                               --  --   --   --   --   --    GENU pectin.sup.4)              --  --   --  --  120 mg                                   --   --   --   --   --    Guaiacol.sup.5)              --  --   --  --  --  80 mg                                        --   --   --   --    L-HPC(LH-31).sup.6)              --  --   --  --  --  --   40 mg                                             --   --   --    L-HPC(LH-21).sup.6)              --  --   --  --  --  --   --   --   --   100 mg    Tragacanth powder              --  --   --  --  --  --   --   60 mg                                                  --   --    Bentonite --  --   --  --  --  --   --   --   200 mg                                                       --    Sodium Carmellose              --  --   --  --  --  --   40 mg                                             --   40 mg                                                       --    Calcium lactate              --  --   --  --   10 mg                                   --   --   --   --   --    Lactose (200M)              204 mg                  54 mg                       124 mg                           114 mg                               114 mg                                   184 mg                                        184 mg                                             204 mg                                                  64 mg                                                       100 mg    D-Mannitol              100 mg                  30 mg                       100 mg                           100 mg                               100 mg                                   80 mg                                        80 mg                                             80 mg                                                  40 mg                                                       127 mg    Avicel RC-591NF               40 mg                  --   --  --  --  --   --   --   --   --    TC-5 "S".sup.7)               6 mg                   6 mg                        6 mg                            6 mg                                6 mg                                    6 mg                                         6 mg                                             6 mg  6 mg    HPC "L".sup.8)              --  --   --  --  --  --   --   --   --    8 mg    Total     400 mg                  400 mg                       400 mg                           400 mg                               400 mg                                   400 mg                                        400 mg                                             400 mg                                                  400 mg                                                       400 mg    __________________________________________________________________________     .sup.1) Sodium starch phosphate     .sup.2) Carrageenin     .sup.3) Carboxymethylated starch     .sup.4) LM pectin     .sup.5) Guar gum     .sup.6) Low substituted hydroxypropyl cellulose     .sup.7) Hydroxypropyl methylcellulose     .sup.8) Hydroxypropyl cellulose

                                      TABLE 5    __________________________________________________________________________    Composition No.              18   19  20  21   22  23  24   25  26   27  28   29    __________________________________________________________________________    Cinnarizine              12.5 12.5                       12.5                           12.5 12.5                                    12.5                                        12.5 12.5                                                 12.5 12.5                                                          50   50    Avicel RC-591NF              32.5 --  --  --   --  --  --   --  --   --  --   --    Pionil 1500.sup.1)              --   35.0                       --  --   --  --  --   --  --   --  --   --    Genu gel SWG-J.sup.2)              --   --  3.75                           2.50 --  --  --   --  --   --  --   --    Locust bean gum              --   --  7.50                           5.00 --  --  --   --  --   --  --   --    Primojel.sup.3)              --   --  --  --   47.5                                    --  --   --  --   --  --   --    GENU pectin.sup.4)              --   --  --  --   --  30.0                                        --   --  --   --  --   --    Calcium lactate              --   --  --  --   --  2.50                                        --   --  --   --  --   --    Guaiacol.sup.5)              --   --  --  --   --  --  25.0 --  --   --  --   --    L-HPC(LH-31).sup.6)              --   --  --  --   --  --  --   17.5                                                 --   --  --   --    Sodium Carmellose              --   --  --  --   --  --  --   17.5                                                 10.0 --  --   --    Bentonite --   --  --  --   --  --  --   --  60.0 --  --   --    Tragacanth powder              --   --  --  --   --  --  --   --  --   20.0                                                          --   --    Matsunorin CM              --   --  --  --   --  --  --   --  --   --  240  --    Matsunorin W              --   --  --  --   --  --  --   --  --   --  --   240    L-HPC (LH-21).sup.6)              --   --  --  25.0 --  --  --   --  --   --  --   --    Lactose (200M)              33.5 31.0                       54.75                           33.5 18.5                                    33.5                                        41.0 31.0                                                 6.00 46.00                                                          74   74    D-Mannitol              20.0 20.0                       20.0                           20.0 20.0                                    20.0                                        20.0 20.0                                                 10.0 20.0                                                          30   30    TC-5 "S".sup.7)              1.50 1.50                       1.50                           1.50 1.50                                    1.50                                        1.50 1.50                                                 1.50 1.50                                                          6    6    Total     100 mg                   100 mg                       100 mg                           100 mg                                100 mg                                    100 mg                                        100 mg                                             100 mg                                                 100 mg                                                      100 mg                                                          400                                                               400    __________________________________________________________________________                                                               mg     .sup.1) Sodium starch phosphate     .sup.2) Carrageenin     .sup.3) Carboxymethylated starch     .sup.4) LM pectin     .sup.5) Guar gum     .sup.6) Low substituted hydroxypropyl cellulose of substitution     .sup.7) Hydroxypropyl methylcellulose

The properties of each of aqueous gel compositions obtained by addingwater to the dry gel compositions of the present invention given inTable 4 in the same manner as that of Example 1 were determined after 60min to obtain the results given in the following Table 6.

                  TABLE 6    ______________________________________    Composition No.               Ratio        First   Second Third    ______________________________________     8         1:2 60 min. after                            162     151    146     9         1:10 60 min. after                            481     454    450    10         1:15 60 min. after                            184     201    244    11         1:3 60 min. after                            1540    929    530    12         1:5 60 min. after                            793     787    772    13         1:5 60 min. after                            389     281    253    14         1:3 60 min. after                            551     568    603    15         1:5 60 min. after                            173     177    166    16         1:3 60 min. after                            897     800    783    17         1:5 60 min. after                            357     352    358    ______________________________________

Industrial Usability

When the dry gel composition of the present invention is mixed with apredetermined quantity of water, a homogeneous gruel-like aqueous gelcomposition is obtained. Even aged people having a weak swallowingfunction can easily swallow the aqueous gel composition thus prepared,without improper sucking into their tracheas. Thus, the dry gelcomposition of the present invention is very useful in their medicalcare. Another characteristic feature of the present invention is thatthe aqueous gel composition can be prepared in a short time by anextremely simple operation at the time of use.

What is claimed is:
 1. A dry gel composition comprising 40% by weight orbelow, based on the whole composition, of a medicine which can be orallyadministered, 3% by weight or above of a gelling agent comprisingpregelatinized starch and 5% by weight or below of a binder, whichcomposition is capable of forming an aqueous gel composition havingviscosity of about 100 to 500 cP and having a consistency of gruel, uponmixing with 2 to 15 parts by weight of water per part by weight of thecomposition at a temperature of 40° C. or below, wherein the medicinewhich can be orally administered is cinnarizine or allopurinol.
 2. Thecomposition according to claim 1 wherein the gelling agent is asubstance capable of forming a gel upon stirring with water in an amountof not larger than the maximum absorption at a temperature of 40° C. orbelow.
 3. The composition according to claim 2 wherein the gelling agentis thixotropic.
 4. The composition according to claim 1 wherein anaqueous gel composition having a consistency of gruel, obtained bymixing 1 part by weight of the composition with 6 to 8 parts by weightof water at a temperature of 40° C. or below has a self-fluidity and aviscosity of 100 to 500 cP.
 5. The composition according to claim 4wherein the aqueous gel composition is thixotropic.
 6. The compositionaccording to claim 1, which has been granulated.
 7. A dry gelcomposition containing 40% by weight or below of a medicine which can beorally administered, 50% by weight or above of pregelatinized starch and5% by weight or below of a binder, which composition is capable offorming an aqueous gel composition having a viscosity of about 100 to500 cP and having a consistency of gruel, upon mixing with 6 to 8 partsby weight of water per part by weight of the composition at atemperature of 40° C. or below.
 8. The composition according to claim 7,which contains 60% by weight or above of pregelatinized starch.
 9. Thecomposition according to claim 7 wherein an aqueous gel compositionobtained by mixing 1 part by weight of the composition with 6 to 8 partsby weight of water at a temperature of 40° C. or below has aself-fluidity and a viscosity of 100 to 500 cp.
 10. The compositionaccording to claim 9 wherein the aqueous gel is thixotropic.
 11. Thecomposition according to claim 7, which has been granulated.
 12. Thecomposition according to claim 7, wherein the medicine which can beorally administered is cinnarizine or allopurinol.